摘要：

Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that have been implicated in signal transduction through tyrosine kinase- and heterotrimeric G-protein-linked receptors. We report herein the cloning and characterization of p110未, a novel class I PI3K. Like p110伪 and p110尾, other class I PI3Ks, p110未 displays a broad phosphoinositide lipid substrate specificity and interacts with SH2/SH3 domain-containing p85 adaptor proteins and with GTP-bound Ras. In contrast to the widely distributed p110伪 and 尾, p110未 is exclusively found in leukocytes. In these cells, p110伪 and 未 both associate with the p85伪 and 尾 adaptor subunits and are similarly recruited to activated signaling complexes after treatment with the cytokines interleukin 3 and 4 and stem cell factor. Thus, these class I PI3Ks appear not to be distinguishable at the level of p85 adaptor selection or recruitment to activated receptor complexes. However, distinct biochemical and structural features of p110未 suggest divergent functional/regulatory capacities for this PI3K. Unlike p110伪, p110未 does not phosphorylate p85 but instead harbors an intrinsic autophosphorylation capacity. In addition, the p110未 catalytic domain contains unique potential protein鈥損rotein interaction modules such as a Pro-rich region and a basic-region leucine-zipper (bZIP)-like domain. Possible selective functions of p110未 in white blood cells are discussed.

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